The measurement of gas concentrations, particularly in blood, is the object of continuing development in the gas analysis field.
The classical Clark electrode technology (Trans. Am. Soc. Artificial Internal Organs (1956) 2:41), which has been applied to oxygen measurement in commercially available blood gas analyzers (see, for example, Weinberg U.S. Pat. No. 4,361,540 and Enzer U.S. Pat. No. 4,871,439), does not use planar microfabrication techniques. The gold working electrode is usually made from a drawn wire, having a diameter of about 10 microns, embedded in glass. The small diameter of the electrode reduces effects of sample flow on the sensor output. It should be emphasized, however, that although this electrode is a "microelectrode," it is not made with planar microfabrication methods. In particular, a gas permeable membrane is stretched over the end of the electrode and secured by an O-ring to enclose and isolate the sensor from the sample solution.
It is also well known that classical (i.e., non-microfabricated) Clark oxygen electrodes exhibit silver contamination of the gold electrode surface during normal use. This contamination arises from silver deposition at the gold cathode. Silver contamination of the gold electrode is problematic for two reasons: (i) it affects the oxygen reduction wave as silver and gold have different catalytic activities, and (ii) halothanes and other common anaesthetic gases exhibit significantly greater electrochemical reduction on silver as compared to gold (see, for example, Hall et al. J. Biomed. Eng. (1988) 10:319), thus, giving rise to a variable interference current.
With standard Clark electrode technology, the basic approach to obviate this problem has been to position the silver-silver chloride electrode within the electrode barrel several centimeters away from the gold electrode. Even so, during use the membrane must occasionally be removed from the electrode and any silver contamination of the gold surface removed by polishing. This approach is clearly impractical for planar microfabricated sensors where the membrane is manufactured as an integral part of the device.
Considering the prior efforts to manufacture planar oxygen sensors, two aspects are noteworthy: first, the reference electrode and the working electrode are generally positioned in close proximity; second, the electrodes are electrically isolated from the sample by a gas permeable membrane that encloses the electrodes.
For example, U.S. Pat. No. 4,062,750 (Butler) describes an alleged microfabrication method for manufacture of a thin-film polarographic oxygen sensor. This reference describes an array of cathodes on a silicon substrate. In the primary embodiment of this reference, (i) the separation between cathodes and anode in only 25 microns (column 4, line 10) and (ii) the silicon device is assembled into a cylindrical element which enables a gas permeable membrane to be secured over the silicon device by means of an O-ring. Thus, the primary embodiment is essentially a hybrid device in which planar microfabrication is used to manufacture the electrodes, while the electrolyte layer and gas permeable membrane are provided in the same manner as the classical Clark electrode. A second embodiment, discussed at column 16 of this reference, allows the establishment of a gas permeable layer via plasma polymerization. Nonetheless, all the oxygen sensing devices described in this reference position the anode and cathode (or array thereof) in close proximity to each other and enclose both electrodes under a gas permeable membrane.
U.S. Pat. No. 4,534,356 (Papadakis) discloses a planar manufacturing method for the fabrication of a solid state transcutaneous blood gas sensor that utilizes an electrode pair. A gas permeable membrane is used to enclose the structure. Here, a material is applied onto the device which dries to leave a membrane that adheres without requiring an O-ring. The patent asserts that the blood oxygen sensor of the alleged invention needs no pool of electrolyte and that the gas permeable membrane need not be changed, thus, avoiding the need for recalibration. The disclosure provides no teaching regarding electrode configuration and placement, beyond showing that the electrodes are positioned next to each other and that both are enclosed by the gas permeable membrane.
European Patent Application No. 0496521 A1 (Tsukuda) discloses a planar laminated structure for blood oxygen measurement which is alleged to provide the desired longer operational lifetime. In the Tsukuda devices, an enlarged electrolyte reservoir 12 is defined by the layered laminated pieces. This enlarged electrolyte reservoir is in contact with the working electrode 84 and reference electrodes 13. (See, FIG. 5.) The specification explains that the electrodes are located in different layers to allow flexibility in the dimensions of the electrodes and which achieve good sensor lifetime. (See, column 4, lines 28-31.) In other words, the reference electrode must be large enough to be consistent with the desired longer operational lifetime. (See, column 4, lines 1-4.) Likewise, the electrolyte capacity is adjusted to select an appropriate lifetime. (See, column 2, lines 41-57.) However, this reference makes no mention of silver contamination of gold. Furthermore, both the working and reference electrodes are enclosed under the gas permeable membrane 7.
U.S. Pat. No. 4,682,602 (Prohaska) teaches a microfabricated sensor design that can allegedly be used for many analytes. A chamber 3, containing an electrode or transducer, is created with an aperture in the chamber wall. (See, for example, FIG. 1.) The aperture ensures that the electrode is not electrically isolated from the sample. However, it is clear that the intention is to create a substantially enclosed structure, as is readily apparent from an examination of FIGS. 1-3 of this reference. At column 3, lines 52-59, the specification states that two electrodes or transducers can be utilized to form an electrochemical cell within the confines of the enclosed chamber. Essentially, this reference describes a microfabricated version of a pin-hole electrode that is well known in the electrochemical sensor art.
U.S. Pat. No. 4,933,048 (Lauks) describes a reference electrode/working electrode configuration in which the working electrode 10 is completely enclosed by an overlayer 13 that is a membrane or series of membranes that render the working electrode specific to a species to be measured. (See, FIG. 2.) Thus, the working electrode is effectively insulated from the reference electrode. This patent also discloses a reference electrode that wets up rapidly from a dry-stored state and comprises a low impedance path to an external solution. The disclosure of this reference is incorporated in its entirety by reference herein.
U.S. Pat. No. 5,096,669 (Lauks) discloses a disposable device, including a housing, sensor, sample retaining means, and sample conduit. The housing also bears a sensor region in which at least one sensor is located. The disclosure of this reference is incorporated in its entirety by reference herein.
Both open and enclosed oxygen sensor structures are disclosed in U.S. Pat. No. 5,200,051 (Cozzette). (See, for example, columns 41-3 and FIGS. 7A and 7B, respectively.) However, the gold and silver/silver chloride electrodes are positioned in close proximity under the same "open" structured gas permeable membrane. The specification does not suggest the problem of gold electrode contamination by the components of the silver/silver chloride reference electrode and, hence, offers no solution for same. Indeed, FIG. 7A illustrates a sensor configuration in which the gold working electrode is flanked by the silver/silver chloride reference electrode. The disclosure of this reference is incorporated in its entirety by reference herein.